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BACKGROUND & AIMS: We investigated whether baseline and on-treatment alanine aminotransferase (ALT) levels during entecavir (ETV) therapy are associated with achieving subcirrhotic liver stiffness (LS) and hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: We analyzed data from 347 treatment-naïve patients with HBV-related cirrhosis, who started ETV between 2006 and 2011 and were followed up for >5 years without developing HCC. The study outcomes were achieving subcirrhotic LS at 5 years of ETV, and risk of HCC development beyond 5 years of ETV. Subcirrhotic LS was defined as <12 kPa by transient elastography. RESULTS: After 5 years of ETV, 227 (65.4%) patients achieved subcirrhotic LS. During a median follow-up of 9.2 years, 49 (14.1%) patients developed HCC beyond 5 years of ETV. ALT levels at baseline, at 1 year of ETV therapy, and 5 years of ETV therapy were not associated with the probability of achieving subcirrhotic LS at 5 years of ETV therapy or risk of HCC development beyond 5 years of ETV therapy (all P > .05). Patients achieving subcirrhotic LS at 5 years of ETV therapy had significantly lower risk of HCC development than those who did not (adjusted hazard ratio, 0.33; 95% confidence interval, 0.17-0.64; P = .001). CONCLUSIONS: Baseline and on-treatment ALT levels were not associated with achieving subcirrhotic LS at 5 years of ETV therapy or with risk of HCC development beyond 5 years of ETV therapy in patients with HBV-related cirrhosis. Achieving subcirrhotic LS at 5 years of ETV therapy was independently associated with lower risk of HCC development beyond 5 years of ETV therapy.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/complicações , Vírus da Hepatite B , Neoplasias Hepáticas/complicações , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Antivirais , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/complicações , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: Cirrhosis and age (CAGE-B) and stiffness and age (SAGE-B) models assess the risk of hepatocellular carcinoma (HCC) development in white patients with chronic hepatitis B (CHB) undergoing sustained antiviral therapy (AVT). Herein, we checked the predictive performance of these models in Asian patients with CHB. METHODS: We reviewed 734 treatment-naive patients with CHB who started entecavir between 2006 and 2011 and were followed up for more than 5 years without HCC development during AVT. The predictive performance of CAGE-B and SAGE-B models was calculated using area under the receiver operating characteristic curves (AUROCs). RESULTS: Median liver stiffness assessed using transient elastography after 5 years of AVT was 6.8 kPa. Median CAGE-B and SAGE-B models after 5 years of AVT were 7.0 and 6.0, respectively. More than 5 years after AVT initiation, 66 patients (9.0%) developed HCC. The AUROCs of the CAGE-B and SAGE-B models were 0.764 and 0.785 after 7 years and 0.799 and 0.802 after 10 years of AVT, respectively. The cumulative incidence of HCC was significantly higher in the high-risk groups according to CAGE-B and SAGE-B risk stratification than in the medium- and low-risk groups (P < .05 in all cases). The SAGE-B model showed a higher likelihood ratio (χ2) (76.2 vs 71.4) and linear trend (χ2) (74.1 vs 58.6) than the CAGE-B model, whereas the CAGE-B model showed higher Akaike information criteria (64.3 vs 50.3). CONCLUSIONS: Both SAGE-B and CAGE-B showed acceptable performance in predicting HCC after 5 years of AVT in Asian patients with CHB.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Guanina/análogos & derivados , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologiaRESUMO
OBJECTIVE: The study sought to estimate the relationship between body surface temperature (BST) and temperature humidity index (THI) and to present the validity of THI as a heat stress index in the field. METHODS: Eight Hanwoo heifers (20 to 32 month) were examined in a field trial, with a space allowance of 10 m2 per head. The BST was measured using an infrared thermographic camera. The BST of five body regions (eyes, hindquarters, nose, part of horns, and ears), ambient temperature (AT), and relative humidity (RH) were measured 7 times daily (07, 09, 11, 13, 15, 17, and 19 h) during each season with three replicates. RESULTS: The THI ranged 34.0 to 56.9 during spring (AT, -1.0°C to 13.4°C), 75.1 to 84.7 during summer (AT, 24.9°C to 33.6°C), 55.8 to 70.9 during autumn (AT, 13.0°C to 26.0°C) and 17.5 to 39.2 during winter (AT, -10.4°C to 1.0°C). In the regression analysis, the coefficient of determination (R2) between THI and BST was 0.88, 0.72, 0.83, 0.86, and 0.85 for the eyes, hindquarters, nose, part of horn, and ears area, respectively. This indicates that BST has a strong correlation with AT and RH. Expression equations were estimated as Y (THI) = 31.54+0.1085X (BST of eyes) and Y (THI) = 30.48+0.1147X (BST of hindquarters) by simple linear regression analysis in this experiment. CONCLUSION: Consequently, the upper bound for heat stress estimation can be specified ranging from THI of 65 (eyes) to 70 (hindquarters). From this we can expect a precise feeding system for Korean native cattle in the field.
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Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA-21 and lncRNA-ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA-21 and higher lncRNA-ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C-reactive protein (all p < 0.05). The overall survival and progression-free survival were significantly lower in patients with higher circulating levels of exosomal miRNA-21 (≥0.09) and lncRNA-ATB (≥0.0016) (log-rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) are novel prognostic markers and therapeutic targets for HCC.
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Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Ácidos Nucleicos Livres/sangue , Neoplasias Hepáticas/sangue , MicroRNAs/sangue , RNA Longo não Codificante/sangue , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Ácidos Nucleicos Livres/metabolismo , Progressão da Doença , Exossomos/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Veia Porta/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , RNA Longo não Codificante/metabolismo , Trombose Venosa/diagnóstico , Trombose Venosa/etiologiaRESUMO
With the rapid advances in single-molecule and live-cell imaging studies to investigate biological problems, the role of chemical probes to monitor reactions in a live cell has considerably increased. However, selective labeling of a target protein or a specific residue is highly challenging due to the high complexity of the biological system. In particular, biological macromolecules (such as proteins, DNA, or RNA) share many functional groups that potentially cross-react with exogenous chemical probes. Thus, there are high demands for perfect biocompatible reactions utilizing biologically unavailable chemistry. Metal-catalyzed reactions have been extensively investigated as synthetic methodology studies, including initial attempts in applying the chemistry in aqueous solutions in vitro or even in biological conditions. Herein, the latest developments and progress in metal-catalyzed bio-orthogonal reactions for biomolecule labeling are summarized.
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DNA/química , Proteínas/química , RNA/química , Metais/química , Coloração e Rotulagem/métodosRESUMO
An accurate method for detecting vital signs obtained from a Doppler radar sensor is proposed. A Doppler radar sensor can remotely obtain vital signs such as heartbeat and respiration rate, but the vital signs obtained by using the sensor do not show clear peaks like in electrocardiography (ECG) because of the operating characteristics of the radar. The proposed peak detection algorithm extracts the vital signs from the raw data. The algorithm shows the mean accuracy of 96.78% compared to the peak count from the reference ECG sensor and a processing time approximately two times faster than the gradient-based algorithm. To verify whether heart rate variability (HRV) analysis similar to that with an ECG sensor is possible for a radar sensor when applying the proposed method, the continuous parameter variations of the HRV in the time domain are analyzed using data processed with the proposed peak detection algorithm. Experimental results with six subjects show that the proposed method can obtain the heart rate with high accuracy but cannot obtain the information for an HRV analysis because the proposed method cannot overcome the characteristics of the radar sensor itself.
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Algoritmos , Radar , Sinais Vitais , Adulto , Eletrocardiografia , Feminino , Frequência Cardíaca , Humanos , Masculino , Taxa Respiratória , Processamento de Sinais Assistido por Computador , Telemetria , Adulto JovemRESUMO
Many intracellular proteins are metabolically unstable, and their half-life was known to be controlled by the "N-end rule," that is, the N-terminal residue controlled protein stability. To visualize or measure the cellular stability of a protein, depending on the N-terminal residues, attention is being paid to the development of selective labeling methods for individual N-terminal amino acids. However, there are only a limited number of functional groups available for specific N-terminal amino acid labeling in a biological environment. Herein, we report a re-examination of salicylaldehyde ester for selective N-terminal residue tagging. Salicylaldehyde ester has been used for chemical ligation to N-terminal serine or threonine under pyridine/acetic acid conditions. Inspired by previous selective serine/threonine labeling, N-terminal labeling of salicylaldehyde ester in aqueous buffer has been examined by using boron-dipyrromethene (BODIPY), rhodamine, and coumarin probes. Surprisingly, the selectivity not only significantly differed, depending on the fluorophore incorporated in salicylaldehyde, but was also perturbed by the addition of a small fraction of phosphate-buffered saline. In particular, the coumarin-based salicylaldehyde ester probe showed notable selectivity against N-terminal cysteine under aqueous buffer conditions. This result reveals the serendipitous discovery of a new N-terminal cysteine labeling strategy.
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Aldeídos/química , Cisteína/química , Ésteres/química , Corantes Fluorescentes/química , Sondas Moleculares/química , Proteínas/química , Soluções Tampão , Cumarínicos/química , FluorescênciaRESUMO
OBJECTIVE: This study compared fatty acid compositions and antioxidant activities of high-preference cuts (loin, tenderloin, and rib) and low-preference cuts (brisket, topside, and shank) of Hanwoo (Bos taurus coreanae) cows to obtain potentially useful information for promoting the consumption of various low-preference cuts. METHODS: Individual 500 g samples of fresh beef were collected from each of the six cuts from 10 Hanwoo cows (quality grade 1) and immediately freeze-dried. The dried samples were evaluated for fatty acid composition, free radical scavenging activities (hydroxyl, alkyl, and 2, 2'-diphenyl-1-picrylhydrazyl [DPPH] radical), and antioxidative enzyme activities (glutathione peroxidase [GPx], glutathione-S-transferase [GST], and superoxide dismutase [SOD]). RESULTS: The percentages of total polyunsaturated fatty acids were significantly higher in low-preference cuts than in high-preference cuts (p<0.05). Hydroxyl, alkyl, and DPPH radical scavenging activities were significantly higher in low-preference cuts than in high-preference cuts (p<0.05). In addition, the activities of antioxidant enzymes, such as GPx, GST, and SOD, were significantly higher in low-preference cuts compared with high-preference cuts (p<0.05). CONCLUSION: These results may influence consumers to include more low-preference cuts in their selections based on the nutritional facts, which could help to balance the beef market in South Korea.
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Chemical probes are powerful tools for interrogating small molecule-target interactions. With additional fluorescence Turn-ON functionality, such probes might enable direct measurements of target engagement in live mammalian cells. DNS-pE (and its terminal alkyne-containing version DNS-pE2) is the first small molecule that can selectively label endogenous 3-phosphoglycerate dehydrogenase (PHGDH) from various mammalian cells. Endowed with an electrophilic vinyl sulfone moiety that possesses fluorescence-quenching properties, DNS-pE/DNS-pE2 became highly fluorescent only upon irreversible covalent modification of PHGDH. With an inhibitory property (inâ vitro Ki =7.4â µm) comparable to that of known PHGDH inhibitors, our probes thus offer a promising approach to simultaneously image endogenous PHGDH activities and study its target engagement in live-cell settings.
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Corantes Fluorescentes/química , Fosfoglicerato Desidrogenase/química , Sulfonas/química , Animais , Células COS , Chlorocebus aethiops , Fluorescência , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Molecular , Espectrometria de FluorescênciaRESUMO
The current gold-standard diagnosis method for avian influenza (AI) is an embryonic egg-based hemagglutination assay followed by immunoblotting or PCR sequencing to confirm subtypes. It requires, however, specialized facilities to handle egg inoculation and incubation, and the subtyping methods relied on costly reagents. Now, the first differential sensing approach to distinguish AI subtypes is demonstrated using series of cell lines and a fluorescent sensor. Susceptibility of AI virus differs depending on genetic backgrounds of host cells. Cells were examined from different organ origins, and the infection patterns against a panel of cells were utilized for AI virus subtyping. To quantify AI infection, a highly cell-permeable fluorescent superoxide sensor was designed to visualize infection. This differential sensing strategy successfully proved discriminations of AI subtypes and demonstrated as a useful primary screening platform to monitor a large number of samples.
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Corantes Fluorescentes/química , Vírus da Influenza A/genética , Células Madin Darby de Rim Canino/virologia , Infecções por Orthomyxoviridae/diagnóstico por imagem , Ácidos Sulfônicos/química , Superóxidos/análise , Animais , Células CHO , Linhagem Celular , Cricetulus , Cães , Humanos , Infecções por Orthomyxoviridae/genética , Superóxidos/metabolismoRESUMO
Tumor initiating cells (TICs) have been implicated in clinical relapse and metastasis of a variety of epithelial cancers, including lung cancer. While efforts toward the development of specific probes for TIC detection and targeting are ongoing, a universal TIC probe has yet to be developed. We report the first TIC-specific fluorescent chemical probe, TiY, with identification of the molecular target as vimentin, a marker for epithelial-to-mesenchymal transition (EMT). TiY selectively stains TICs over differentiated tumor cells or normal cells, and facilitates the visualization and enrichment of functionally active TICs from patient tumors. At high concentration, TiY also shows anti-TIC activity with low toxicity to non-TICs. With the unexplored target vimentin, TiY shows potential as a first universal probe for TIC detection in different cancers.
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Corantes Fluorescentes/química , Células-Tronco Neoplásicas/patologia , Bibliotecas de Moléculas Pequenas/química , Vimentina/análise , Animais , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Pulmonares/patologia , CamundongosRESUMO
BACKGROUND AND AIM: Liver stiffness (LS) value determined using transient elastography (TE) can be used to assess the degree of liver fibrosis. The study investigated whether TE can predict the recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). METHODS: This study retrospectively enrolled 228 patients with HCC who received TE and RFA as the first-line treatment for HCC between 2008 and 2015. Cox regression analysis was used to identify independent predictors of HCC recurrence. RESULTS: The median age of the study population (170 men and 58 women) was 61 years. During the study period, HCC recurrence and mortality developed in 125 (54.8%) and 37 (16.2%) patients after RFA, respectively. Liver cirrhosis, platelet count, multiple tumors, and LS value were the independent predictors of HCC recurrence. When the study population was stratified into early (< 12 months) and late (≥ 12 months) recurrence groups, LS value was an independent predictor of late recurrence, along with liver cirrhosis and spleen diameter. The risk of late recurrence was higher in patients with LS values of ≥ 13 kPa than in those with LS values of < 13 kPa (adjusted hazard ratio [HR] = 4.507, 95% confidence interval [CI] 2.131-7.724, P < 0.001). Recurrence was the only predictor of overall survival (HR = 18.583, 95% CI 2.424-142.486, P = 0.005). CONCLUSIONS: Findings of this study suggest that LS measurement using TE can be a useful predictor of HCC recurrence after RFA.
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Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Fígado/diagnóstico por imagem , Recidiva Local de Neoplasia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: This research analyzed behavioral characteristics of Hanwoo (Bos taurus coreanae) steers during each season and growth stage to enable measurement of the animals' welfare level for precision livestock farming. METHODS: A hundred-eight beef steers were divided into three equal groups at a Hanwoo farm according to their growth stage: growing stage (GS), 8 months; early-fattening stage (EFS), 19 months; and late-fattening stage (LFS), 30 months. Twelve behavioral categories were continuously recorded for 13 day-time hours in each four seasons with three replications. RESULTS: Time spent standing was found to be significantly longer in summer at all growth stages (p<0.05). Hanwoos at the GS spent significantly longer standing time in spring and summer than those at the EFS and LFS (p<0.05). Lying time in summer was the shortest for all growth stages (p<0.05). Steers at the LFS spent significantly longer lying time than that at the GS (p<0.05) in summer. For GS and EFS, time spent eating in spring and autumn were longer than in summer and winter (p<0.05). Eating time was the longest for the GS in spring, autumn, and winter, excluding for the LFS in winter (p<0.05). Regarding ruminating, steers at the LFS spent significantly shorter time than those at other stages in all seasons (p<0.05). GS and EFS steers showed the longest walking time in summer compared with other seasons (p<0.05). At GS and LFS, drinking time in summer was the longest of all seasons (p<0.05). Sleeping time was significantly shorter in summer compared with the other seasons (p<0.05). Self-grooming time was the longest in winter for all growth stages (p<0.05). CONCLUSION: Steers were found to have more variable behavioral patterns during summer and the GS and less active behaviors during the LFS, thus extra care seems necessary during the GS, LFS, and summer period.
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OBJECTIVE: This experiment was to determine proper physical traits in the diet for goats by investigating the effects of physically effective neutral detergent fiber (peNDF) content on dry matter intake (DMI), digestibility, and chewing activity in black goats fed with total mixed ration (TMR). METHODS: Six growing wethers of Korean native black goats (Capra hircus coreanae) aged 8 months and weighing between 26.9 kg and 27.1 kg (27.03±5.05 kg) were used in this experiment. Three diets of varying peNDF content were obtained by original TMR (T1), 12,000 rpm grinding (T2), and 15,500 rpm grinding (T3) of the same TMR diet. The peNDF1.18 content of the experimental diets was 23.85%, 21.71%, and 16.22% for T1, T2, and T3, respectively. RESULTS: Average daily gain (ADG) was higher in T2 group compared to those of the control and T3 groups, but ADG and DMI were not affected by the dietary particle size and peNDF content. Also, there was no difference between apparent nutrient digestibility of dry matter, crude fiber, ether extract, neutral detergent fiber, and acid detergent fiber. Although there was no significant difference, rumination and total chewing time were associated with decreased peNDF content. CONCLUSION: The feeding of peNDF-based TMR showed no impact on apparent nutrient digestibility and nitrogen balance. Further studies are required with a wider range of dietary peNDF level and particle size to better identify the effect of dietary peNDF and particle size on chewing activity and performance in goats.
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Affinity-based probes (AfBPs) provide a powerful tool for large-scale chemoproteomic studies of drug-target interactions. The development of high-quality probes capable of recapitulating genuine drug-target engagement, however, could be challenging. "Minimalist" photo-crosslinkers, which contain an alkyl diazirine group and a chemically tractable tag, could alleviate such challenges, but few are currently available. Herein, we have developed new alkyl diazirine-containing photo-crosslinkers with different bioorthogonal tags. They were subsequently used to create a suite of AfBPs based on GW841819X (a small molecule inhibitor of BRD4). Through inâ vitro and inâ situ studies under conditions that emulated native drug-target interactions, we have obtained better insights into how a tag might affect the probe's performance. Finally, SILAC-based chemoproteomic studies have led to the discovery of a novel off-target, APEX1. Further studies showed GW841819X binds to APEX1 and caused up-regulation of endogenous DNMT1 expression under normoxia conditions.
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Reagentes de Ligações Cruzadas/química , Proteínas Nucleares/antagonistas & inibidores , Processos Fotoquímicos , Proteômica , Fatores de Transcrição/antagonistas & inibidores , Proteínas de Ciclo Celular , HumanosRESUMO
BACKGROUND: As a minimally invasive treatment, ethanol sclerotherapy has been used for large symptomatic hepatic cysts, but there are not many long-term reports on treatment outcomes and safety. PURPOSE: To evaluate the long-term outcomes of percutaneous ethanol sclerotherapy in patients with large symptomatic hepatic cysts. MATERIAL AND METHODS: This study included 43 symptomatic, enlarging hepatic cysts in 42 patients who had undergone ethanol sclerotherapy from 2003 to 2013 and were followed up for >1 year. The treatment outcomes were evaluated in terms of the reduction of cyst size and resolution of symptoms. The patients were followed up for a mean period of 33 months with either ultrasound or computed tomography examination. RESULTS: Thirty-nine hepatic cysts (91%) were successfully treated with ethanol sclerotherapy, showing resolution of symptoms and remarkable reduction in cyst volume. Eight hepatic cysts (19%) disappeared completely, and 31 hepatic cysts (72%) decreased in size during the follow-up period. The mean diameter of the cysts decreased from 12.5 ± 4.4 cm to 3.8 ± 3.4 cm during follow-up. There were no immediate serious complications related to the procedure. There were four cases (9%) of treatment failure requiring subsequent surgical procedures. CONCLUSION: Percutaneous ethanol sclerotherapy can be considered as an effective first-line treatment for large symptomatic hepatic cysts.
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Cistos/terapia , Etanol/uso terapêutico , Hepatopatias/terapia , Soluções Esclerosantes/uso terapêutico , Escleroterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistos/diagnóstico por imagem , Diagnóstico por Imagem , Feminino , Seguimentos , Humanos , Hepatopatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The objective of this study was to determine the effects of physically effective neutral detergent fiber (peNDF) content in total mixed ration (TMR) on dry matter intake, digestibility, and chewing activity in fattening Hanwoo (Bos taurus coreanae) heifers. The experiment was designed as a replicated 3×3 Latin square using 12 heifers. Fattening heifers were offered one of three diets [high (T1), medium (T2), and low (T3) peNDF] obtained by different mixing times (3, 10, and 25 min) for the same TMR feed. The peNDF content of TMR was determined by multiplying the proportion of dry matter retained by a 1.18 mm-screen in a Penn State Particle Separator by the dietary NDF content. The peNDF1.18 content was 30.36%, 29.20%, and 27.50% for the T1, T2, and T3 diets, respectively (p<0.05). Dry matter intake was not affected by peNDF content in TMR. Total weight gain in T1 group was significantly higher (p<0.05) than in T2 and T3 groups. However, weight gain did not differ between T2 and T3 groups. The feed conversion ratio decreased with an increase in the peNDF content (T1: 12.18, T2: 14.17, and T3: 14.01 g/g). An increase in the peNDF content of TMR was associated with a linear increase in the digestibility of dry matter, crude protein, crude fiber, neutral detergent fiber, and acid detergent fiber (p<0.05). Also, an increase in peNDF content of the TMR resulted in a linear increase in the number of chews in eating and ruminating (p<0.05), and consequently in the number of total chews (p<0.05). These results indicate that peNDF content affects digestibility and chewing activity. Consequently, the peNDF content of TMR should be considered for improving feed efficiency, digestibility, body weight gain, and performance in fattening heifers.
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BACKGROUND & AIMS: An atypical orphan nuclear receptor small heterodimer partner (SHP) is known to be regulated by AMP-activated protein kinase (AMPK). Both of them inhibit TGF-ß and Smad signalling and exhibit antifibrotic activity in the liver. However, little is known about the protective effects of SHP and AMPK against hepatitis c virus (HCV)-induced hepatic fibrosis. METHODS: Levels of SHP, p-AMPK and fibrotic markers in HCV-infected human liver and in Huh-7.5 cells infected with HCV genotype 2a (JFH-1) were investigated. The effect of adenovirus-mediated overexpression of SHP (Ad-SHP) and AMPK activation via metformin and 5-amino-1-b-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) on fibrotic gene expression was evaluated in HCV-infected cells. Finally, we examined the effect of Ad-SHP and AMPK activators on invasion and activation of LX2 human HSCs induced by conditioned media from HCV-infected hepatocyte (CM). RESULTS: In HCV-infected human livers and Huh-7.5 cells infected with HCV, SHP mRNA and protein levels were diminished compared with controls, whereas profibrotic factors were increased. Pharmacological AMPK activation recovered SHP expression, and Ad-SHP inhibited HCV-induced fibrotic gene expression. This finding was accompanied by inhibition of HCV-stimulated nuclear factor-kappa B, an inducer of TGF-ß. Moreover, CytoSelect invasion assay revealed that enhanced activity and invasiveness of hepatic stellate cells induced by CM. CONCLUSION: These results demonstrate that overexpression of SHP and activation of AMPK reverses profibrogenic features of HCV-infected cells by decreasing TGF-ß and fibrotic gene expression. These findings provide a rationale for SHP as a possible therapeutic target against HCV-induced hepatic fibrosis.
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Proteínas Quinases Ativadas por AMP/metabolismo , Cirrose Hepática/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Linhagem Celular Tumoral , Gluconeogênese/efeitos dos fármacos , Hepacivirus , Células Estreladas do Fígado/metabolismo , Humanos , Metformina/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Ribonucleotídeos/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
PURPOSE: This study aimed to identify research trends related to emotional leadership among nurse managers by conducting a systematic literature review and meta-analysis. This study sought to derive insights that could contribute to improving emotional leadership in nursing practice. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Databases including PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Research Information Sharing Service, Koreanstudies Information Service System, Korean Medical Database, KoreaMed, ScienceON, and DBpia were searched to obtain papers published in English and Korean. Literature searches and screenings were conducted for the period December 1, 2023 to December 17, 2023. The effect size correlation (ESr) was calculated for each variable and the meta-analysis was performed using the statistical software SPSS 29.0, R 4.3.1. RESULTS: Twenty-five (four personal, six job, and fifteen organizational) relevant variables were identified through the systematic review. The results of the meta-analysis showed that the total overall effect size was ESr = .33. Job satisfaction (ESr = .40) and leader-member exchange (ESr = .75) had the largest effect size among the job and organizational-related factors. CONCLUSION: Emotional leadership helps promote positive changes within organizations, improves organizational effectiveness, and increases member engagement and satisfaction. Therefore, it is considered an important strategic factor in improving organizational performance.
Assuntos
Emoções , Satisfação no Emprego , Liderança , Enfermeiros Administradores , Humanos , Bases de Dados Factuais , Enfermeiros Administradores/psicologiaRESUMO
BACKGROUND: Acute kidney injury (AKI) causes distant liver injury, to date, which causes poor outcomes of patients with AKI. Many studies have been performed to overcome AKI-associated liver injury. However, those studies have mainly focused on hepatocytes, and AKI-induced liver injury still remains a clinical problem. Here, we investigated the implication of cholangiocytes and their primary cilia which are critical in final bile secretion. Cholangiocyte, a lining cell of bile ducts, are the only liver epithelial cell containing primary cilium (a microtubule-based cell surface signal-sensing organelle). METHODS: Cystathione γ-lyase (CSE, a transsulfuration enzyme) deficient and wild-type mice were subjected to kidney ischemia followed by reperfusion (KIR). Some mice were administered with N-acetyl-cysteine (NAC). RESULTS: KIR damaged hepatocytes and cholagiocytes, disrupted cholangiocytes primary cilia, released the disrupted ciliary fragments into the bile, and caused abnormal bile secretion. Glutathione (GSH) and H2S levels in the livers were significantly reduced by KIR, resulting in increased the ratio oxidized GSH to total GSH, and oxidation of tissue and bile. CSE and cystathione ß-synthase (CBS) expression were lowered in the liver after KIR. NAC administration increased total GSH and H2S levels in the liver and attenuated KIR-induced liver injuries. In contrast, Cse deletion caused the reduction of total GSH levels and worsened KIR-induced liver injuries, including primary cilia damage and abnormal bile secretion. CONCLUSIONS: These results indicate that KIR causes cholangiocyte damage, cholangiocytes primary cilia disruption, and abnormal bile secretion through reduced antioxidative ability of the liver.